This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to use Peptide Nucleic Acid (PNA) -encoded combinatorial peptide libraries as a tool to perform high-throughput screening for ligands of DNA-binding proteins. In order to synthesize the PNA and amino acid chains in the same reaction vessel, they must be protected by different chemical groups. This has encouraged us to synthesize a non-commercially available PNA, since chemically protected amino acids are readily available. The multistep synthesis of chemically protected PNA monomers will require evaluation of the small molecule products at each reaction step.